Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate.

Détails

Ressource 1Télécharger: 30581889_BIB_867BE52AD282.pdf (5078.56 [Ko])
Etat: Serval
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_867BE52AD282
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate.
Périodique
Molecular therapy. Methods & clinical development
Auteur(s)
György B., Meijer E.J., Ivanchenko M.V., Tenneson K., Emond F., Hanlon K.S., Indzhykulian A.A., Volak A., Karavitaki K.D., Tamvakologos P.I., Vezina M., Berezovskii V.K., Born R.T., O'Brien M., Lafond J.F., Arsenijevic Y., Kenna M.A., Maguire C.A., Corey D.P.
ISSN
2329-0501 (Print)
ISSN-L
2329-0501
Statut éditorial
Publié
Date de publication
14/06/2019
Peer-reviewed
Oui
Volume
13
Pages
1-13
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Hereditary hearing loss often results from mutation of genes expressed by cochlear hair cells. Gene addition using AAV vectors has shown some efficacy in mouse models, but clinical application requires two additional advances. First, new AAV capsids must mediate efficient transgene expression in both inner and outer hair cells of the cochlea. Second, to have the best chance of clinical translation, these new vectors must also transduce hair cells in non-human primates. Here, we show that an AAV9 capsid variant, PHP.B, produces efficient transgene expression of a GFP reporter in both inner and outer hair cells of neonatal mice. We show also that AAV9-PHP.B mediates almost complete transduction of inner and outer HCs in a non-human primate. In a mouse model of Usher syndrome type 3A deafness (gene <i>CLRN1</i> ), we use AAV9-PHP.B encoding <i>Clrn1</i> to partially rescue hearing. Thus, we have identified a vector with promise for clinical treatment of hereditary hearing disorders, and we demonstrate, for the first time, viral transduction of the inner ear of a primate with an AAV vector.
Mots-clé
AAV, adeno-associated virus vector, cochlea, gene delivery, hair cells, hereditary deafness, inner ear, non-human primate
Pubmed
Open Access
Oui
Création de la notice
20/01/2019 17:04
Dernière modification de la notice
29/05/2019 7:09
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